ArticleNature methods2023
Large-scale benchmarking of circRNA detection tools reveals large differences in sensitivity but not in precision.
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Article in Nature methods, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 76 papers.
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76 citing papers in PubMed.
- Toward precision oncology: deciphering the circRNA-EMT axis in cancer and its therapeutic implications.RNA biology · 2026Review
- Review
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- Updated guide to RNA quantification by RNA sequencing and reverse transcription-qPCR.Molecules and cells · 2026Article
- Detecting and quantifying circular RNAs in terabyte-scale RNA-seq datasets with CIRI3.Nature biotechnology · 2026Article
- Assessing the impact of parental linear gene normalization on the performance of statistical models for circular RNA differential expression analysis.Briefings in bioinformatics · 2026Article
- CircRNA profiles from one-tube multiplex probe-based qPCR can distinguish between monozygotic twins.International journal of legal medicine · 2026Article
- Circular RNAs in Lotus japonicus Responses to Nutrient Supply and Mesorhizobium Symbiosis.Plant, cell & environment · 2026Article
- Extracellular-Vesicle-Associated Nucleic Acids in the Diagnosis and Treatment of Respiratory Diseases: A Narrative Review.Pharmaceutics · 2026Review
- Recent advances in the detection and functional analysis of circRNAs with short-read RNA sequencing-based methods.Molecular biology reports · 2026Review
- Role of circular RNAs in regulating toxicity induced by cancer therapies.Genes & diseases · 2026Review
- Protocol for total RNA sequencing analysis of extracellular RNA from biofluids.STAR protocols · 2026Article
- Nanopore direct RNA sequencing and the epitranscriptome: Advances in mapping native RNA landscapes.iMeta · 2026Review
- Plasma cell-free transcriptome profiling in blood plasma from chronic liver disease patients.Scientific data · 2026Article
- A 15-layer multi-omics analysis of gastric cancer ecotypes provides therapeutic insights.Cell reports. Medicine · 2026Article
- Novel Insights into the Role of circRNAs in Cancer Immunotherapy Resistance and Clinical Implications.International journal of molecular sciences · 2026Review
- Landscape of circular RNAs in acute myeloid leukemia and their clinical significance.NPJ precision oncology · 2026Article
- Elucidating the coordination of RNA processing using short-read and long-read RNA-sequencing methods.Nature reviews. Molecular cell biology · 2026Review
- CircRNAs: Novel biomarkers and therapeutic targets for diseases of the central nervous system.Biochemistry and biophysics reports · 2026Review
- Therapeutic rewiring of ceRNA networks: a computational pipeline for drug repurposing in acute kidney injury via circRNA-miRNA-mRNA axis disruption.Human genomics · 2026Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
36 authors.
Marieke VrommanOncoRNALab, Cancer Research Institute Ghent (CRIG), Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.ORCID http://orcid.org/0000-0002-0163-0675
Jasper AnckaertOncoRNALab, Cancer Research Institute Ghent (CRIG), Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.ORCID http://orcid.org/0000-0001-8144-4639
Stefania BortoluzziDepartment of Molecular Medicine, University of Padova, Padova, Italy.
Alessia BuratinDepartment of Molecular Medicine, University of Padova, Padova, Italy.
Chia-Ying ChenGenomics Research Center, Academia Sinica, Taipei City, Taiwan.
Qinjie ChuInstitute of Crop Science and Institute of Bioinformatics, Zhejiang University, Zhejiang, China.
Trees-Juen ChuangGenomics Research Center, Academia Sinica, Taipei City, Taiwan.ORCID http://orcid.org/0000-0002-9661-6672
Roozbeh DehghannasiriDepartment of Biomedical Data Science and of Biochemistry, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-7413-3437
Christoph DieterichKlaus Tschira Institute for Integrative Computational Cardiology, Department of Internal Medicine III, University Hospital Heidelberg, German Center for Cardiovascular Research (DZHK), Heidelberg, Germany.ORCID http://orcid.org/0000-0001-9468-6311
Xin DongSchool of Basic Medical Science, Department of Medical Genetics, Wuhan University, Wuhan, China.
Paul FlicekEMBL-EBI, Hinxton, UK.ORCID http://orcid.org/0000-0002-3897-7955
Enrico GaffoDepartment of Molecular Medicine, University of Padova, Padova, Italy.ORCID http://orcid.org/0000-0001-6338-7677
Wanjun GuCollaborative Innovation Center of Jiangsu Province of Cancer Prevention and Treatment of Chinese Medicine, School of Artificial Intelligence and Information Technology, Nanjing University of Chinese Medicine, Nanjing, China.
Chunjiang HeSchool of Basic Medical Science, Department of Medical Genetics, Wuhan University, Wuhan, China.ORCID http://orcid.org/0000-0002-4868-331X
Steve HoffmannComputational Biology Group, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany.
Osagie IzuoguEMBL-EBI, Hinxton, UK.ORCID http://orcid.org/0000-0003-3116-2558
Michael S JacksonBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK.
Tobias JakobiTranslational Cardiovascular Research Center, University of Arizona - College of Medicine Phoenix, Phoenix, AZ, USA.ORCID http://orcid.org/0000-0002-3906-0401
Eric C LaiSloan Kettering Institute, New York, NY, USA.ORCID http://orcid.org/0000-0002-8432-5851
Justine NuytensOncoRNALab, Cancer Research Institute Ghent (CRIG), Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.ORCID http://orcid.org/0000-0002-4878-1200
Julia SalzmanDepartment of Biomedical Data Science and of Biochemistry, Stanford University, Stanford, CA, USA.
Mauro Santibanez-KorefBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK.
Peter StadlerBioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, Universität Leipzig, Leipzig, Germany.ORCID http://orcid.org/0000-0002-5016-5191
Olivier ThasData Science Institute, I-Biostat, Hasselt University, Hasselt, Belgium.ORCID http://orcid.org/0000-0001-6442-4089
Eveline Vanden EyndeOncoRNALab, Cancer Research Institute Ghent (CRIG), Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.ORCID http://orcid.org/0000-0003-0454-4171
Kimberly VerniersOncoRNALab, Cancer Research Institute Ghent (CRIG), Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.
Guoxia WenState Key Laboratory of Bioelectronics, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, China.
Jakub WestholmDepartment of Biochemistry and Biophysics, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Stockholm University, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-6849-6220
Li YangCenter for Molecular Medicine, Children's Hospital, Fudan University and Shanghai Key Laboratory of Medical Epigenetics, International Laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Fudan, China.ORCID http://orcid.org/0000-0001-8833-7473
Chu-Yu YeInstitute of Crop Science and Institute of Bioinformatics, Zhejiang University, Zhejiang, China.ORCID http://orcid.org/0000-0003-0903-0356
Nurten YigitOncoRNALab, Cancer Research Institute Ghent (CRIG), Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.ORCID http://orcid.org/0000-0003-1183-8688
Guo-Hua YuanCAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0000-0002-8459-3784
Jinyang ZhangBeijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.ORCID http://orcid.org/0000-0002-5163-894X
Fangqing ZhaoBeijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.ORCID http://orcid.org/0000-0002-6216-1235
Jo VandesompeleOncoRNALab, Cancer Research Institute Ghent (CRIG), Department of Biomolecular Medicine, Ghent University, Ghent, Belgium. jo.vandesompele@ugent.be.ORCID http://orcid.org/0000-0001-6274-0184
Pieter-Jan VoldersOncoRNALab, Cancer Research Institute Ghent (CRIG), Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.ORCID http://orcid.org/0000-0002-2685-2637
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MSelective regulatory and biogenesis mechanisms for microRNAsR01GM083300 · NIGMS · SLOAN-KETTERING INST CAN RESEARCH · PI Eric C Lai · 2007 to 2026
$9.8MMechanism and regulation of Hu family RNA binding proteins during neural alternative polyadenylationR01NS083833 · NINDS · SLOAN-KETTERING INST CAN RESEARCH · PI LAI, ERIC C · 2014 to 2023
$5.4MNCI NIH HHS P30 CA008748NIGMS NIH HHS R01 GM083300NIH HHS P30-CA008748NIH HHS R01-NS083833NINDS NIH HHS R01 NS083833Wellcome TrustWellcome Trust WT108749/Z/15/Z
Abstract
The detection of circular RNA molecules (circRNAs) is typically based on short-read RNA sequencing data processed using computational tools. Numerous such tools have been developed, but a systematic comparison with orthogonal validation is missing. Here, we set up a circRNA detection tool benchmarking study, in which 16 tools detected more than 315,000 unique circRNAs in three deeply sequenced human cell types. Next, 1,516 predicted circRNAs were validated using three orthogonal methods. Generally, tool-specific precision is high and similar (median of 98.8%, 96.3% and 95.5% for qPCR, RNase R and amplicon sequencing, respectively) whereas the sensitivity and number of predicted circRNAs (ranging from 1,372 to 58,032) are the most significant differentiators. Of note, precision values are lower when evaluating low-abundance circRNAs. We also show that the tools can be used complementarily to increase detection sensitivity. Finally, we offer recommendations for future circRNA detection and validation.
Indexed as
BenchmarkingRNA, CircularHumansRNASequence Analysis, RNARNARNA, Circular
Identifiers
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